Insulin Resistance

What It Is

Insulin resistance is a metabolic condition where cells throughout the body become less responsive to insulin, the hormone that regulates blood sugar (glucose) uptake. When cells don't respond effectively to insulin's signals, the pancreas compensates by producing more insulin—creating a state of high insulin (hyperinsulinemia) even when blood sugar levels may still appear normal.

How insulin normally works:

1. You eat food → blood sugar rises
2. Pancreas releases insulin → signals cells to absorb glucose from bloodstream
3. Cells respond → glucose enters cells for energy or storage
4. Blood sugar normalizes → insulin levels drop

What happens with insulin resistance:

1. You eat food → blood sugar rises
2. Pancreas releases insulin → but cells don't respond efficiently
3. Blood sugar stays elevated → pancreas releases MORE insulin to force cells to respond
4. High insulin levels persist → creates cascade of metabolic and hormonal effects
5. Over time, pancreas becomes exhausted → can lead to prediabetes or type 2 diabetes

Where insulin resistance develops:

• Muscle cells → less efficient glucose uptake → reduced energy, fatigue
• Fat cells (adipocytes) → insulin promotes fat storage, inhibits fat burning → weight gain (especially abdominal)
• Liver → insulin normally suppresses glucose production; with resistance, liver continues producing glucose → blood sugar stays high
• Brain → insulin affects appetite, mood, cognition; resistance may contribute to brain fog, cravings

Why it develops:

Insulin resistance is multifactorial, influenced by:

• Genetics → family history increases risk
• Diet → high intake of refined carbohydrates, sugar, processed foods
• Sedentary lifestyle → lack of physical activity reduces insulin sensitivity
• Excess body fat (especially visceral/abdominal fat) → fat cells release inflammatory signals that interfere with insulin signaling
• Chronic stress → cortisol promotes insulin resistance
• Poor sleep → disrupts metabolic hormones, reduces insulin sensitivity
• Hormonal changes → declining estrogen during perimenopause/menopause significantly worsens insulin resistance
• Aging → insulin sensitivity naturally declines with age

Why It Matters During Perimenopause/Menopause

Insulin resistance is extremely common during perimenopause and menopause—and it's often the hidden driver behind stubborn weight gain, energy crashes, and worsening metabolic health.

Estrogen's protective role:

During reproductive years, estrogen helps maintain insulin sensitivity through multiple mechanisms:

• Enhances glucose uptake in muscle cells
• Reduces visceral (abdominal) fat accumulation
• Supports healthy fat distribution (more subcutaneous, less visceral)
• Reduces inflammation (which interferes with insulin signaling)
• Supports mitochondrial function (energy production in cells)

When estrogen declines:

• Insulin sensitivity decreases → cells become less responsive to insulin
• Visceral fat increases → abdominal fat accumulates (the classic "menopause belly")
• Fat distribution shifts → from hips/thighs (subcutaneous) to abdomen (visceral)
• Inflammation increases → visceral fat releases inflammatory cytokines that worsen insulin resistance
• Metabolic rate slows → easier to gain weight, harder to lose it

The result:

Many women who had normal blood sugar and stable weight throughout their 30s and early 40s suddenly develop:

• Abdominal weight gain (even without changes to diet or exercise)
• Difficulty losing weight (strategies that used to work no longer do)
• Energy crashes (especially after meals)
• Intense cravings (for sugar, carbs)
• Brain fog (blood sugar swings affect cognition)
• Worsening cholesterol (insulin resistance affects lipid metabolism)
• Elevated blood pressure (insulin resistance is linked to hypertension)

The vicious cycle:

Insulin resistance creates a self-reinforcing loop:

1. Estrogen declines → insulin sensitivity decreases
2. Insulin resistance develops → more insulin produced → promotes fat storage (especially visceral)
3. Visceral fat increases → releases inflammatory signals → worsens insulin resistance
4. High insulin lowers SHBG (sex hormone binding globulin) → increases free testosterone and estrogen
5. Hormonal imbalances worsen → symptoms intensify
6. Cycle continues

The metabolic syndrome connection:

Insulin resistance is a core feature of metabolic syndrome, a cluster of conditions that increase risk for heart disease, stroke, and type 2 diabetes:

• Abdominal obesity (waist circumference > 35 inches for women)
• Elevated blood sugar (fasting glucose > 100 mg/dL or A1C > 5.7%)
• Elevated triglycerides (> 150 mg/dL)
• Low HDL cholesterol (< 50 mg/dL for women)
• Elevated blood pressure (> 130/85 mmHg)

Having 3 or more of these criteria = metabolic syndrome. Many women develop this during perimenopause/menopause.

How It Works

Mechanism of insulin resistance:

Insulin resistance develops at the cellular level when insulin receptors and downstream signaling pathways become impaired:

1. Insulin binds to receptors on cell surface (normally)
2. Receptor signaling is impaired → cells don't respond efficiently
3. Glucose transporters (GLUT4) don't mobilize → glucose can't enter cells
4. Blood sugar stays elevated → pancreas releases more insulin
5. Chronic high insulin creates additional problems (fat storage, inflammation, hormonal disruption)

Why signaling becomes impaired:

• Chronic inflammation → inflammatory cytokines (especially from visceral fat) interfere with insulin receptor signaling
• Lipid accumulation in cells → excess fat in muscle and liver cells disrupts insulin signaling
• Mitochondrial dysfunction → impaired energy production reduces cells' ability to use glucose
• Oxidative stress → damages cellular machinery, including insulin receptors
• Hormonal imbalances → low estrogen, high cortisol, low thyroid all contribute

Insulin resistance affects other hormones:

Insulin + SHBG (sex hormone binding globulin):

• High insulin lowers SHBG → SHBG binds to sex hormones (testosterone, estrogen) and keeps them inactive
• Low SHBG = more free (active) testosterone → can cause acne, facial hair, scalp hair loss (androgen excess symptoms)
• Low SHBG = more free estrogen → can worsen estrogen dominance symptoms (in early perimenopause)

Insulin + Testosterone:

• High insulin stimulates ovaries to produce more testosterone (even in perimenopause/menopause)
• Combined with low SHBG → androgen dominance symptoms: acne, oily skin, hirsutism (facial/body hair), scalp hair thinning

Insulin + Cortisol:

• Chronic stress raises cortisol → cortisol promotes insulin resistance (raises blood sugar, reduces insulin sensitivity)
• High insulin raises cortisol → creates stress response, disrupts sleep
• Vicious cycle: stress worsens insulin resistance, insulin resistance worsens stress response

Insulin + Thyroid:

• Insulin resistance can impair conversion of T4 (inactive thyroid hormone) to T3 (active form)
• Can worsen hypothyroid symptoms (fatigue, weight gain, brain fog, hair loss)

Insulin + Leptin (satiety hormone):

• Insulin resistance often coexists with leptin resistance → leptin signals "I'm full," but brain doesn't respond
• Result: Increased hunger, cravings, difficulty recognizing satiety → overeating, weight gain

Insulin + Inflammation:

• High insulin promotes inflammation (via multiple pathways)
• Inflammation worsens insulin resistance
• Chronic low-grade inflammation is linked to virtually all chronic diseases (heart disease, cancer, Alzheimer's, autoimmune conditions)

What It Looks Like

Early Insulin Resistance (Often Undetected)

Physical:

• Abdominal weight gain → especially visceral fat ("apple shape"), even if overall weight is stable
• Difficulty losing weight → despite diet/exercise efforts that used to work
• Energy crashes after meals → especially after high-carb meals (blood sugar spike → insulin surge → blood sugar crash)
• Increased hunger and cravings → especially for sugar, carbs, or frequent snacking
• Skin changes → darkening/thickening of skin in body folds (neck, armpits, groin)—called acanthosis nigricans, a hallmark of insulin resistance
• Skin tags → small, benign growths (often around neck, armpits)—associated with insulin resistance

Cognitive:

• Brain fog → difficulty concentrating, especially when hungry or after high-carb meals
• Reduced mental stamina → cognitive fatigue, slower processing

Emotional:

• Mood swings → blood sugar fluctuations affect mood stability
• Irritability when hungry ("hanger") → blood sugar dysregulation intensifies emotional reactivity
• Anxiety → blood sugar crashes can trigger anxiety, sense of dread

Metabolic (Lab Markers):

• Fasting glucose: 100-125 mg/dL (prediabetes range; normal is < 100 mg/dL)
• A1C: 5.7-6.4% (prediabetes range; normal is < 5.7%)
• Fasting insulin: > 10-15 mIU/L (high; normal is < 10 mIU/L, optimal is < 5 mIU/L)
• HOMA-IR (calculated from fasting glucose and insulin): > 2.0 indicates insulin resistance
• Triglycerides: Elevated (> 150 mg/dL)
• HDL cholesterol: Low (< 50 mg/dL)
• Triglyceride-to-HDL ratio: > 2 (marker of insulin resistance)

Advanced Insulin Resistance / Metabolic Syndrome

Physical:

• Significant abdominal obesity → waist circumference > 35 inches
• Persistent fatigue → cells can't use glucose efficiently → energy deficiency
• Frequent urination, increased thirst → early signs of high blood sugar
• Acne, oily skin → high insulin lowers SHBG → androgen excess
• Facial hair growth, scalp hair thinning → androgen dominance
• High blood pressure → insulin resistance affects vascular health
• Fatty liver (non-alcoholic fatty liver disease/NAFLD) → insulin resistance promotes fat accumulation in liver

Cognitive:

• Severe brain fog → impaired glucose metabolism affects brain function
• Memory problems → insulin resistance is linked to increased Alzheimer's risk (sometimes called "type 3 diabetes")

Metabolic (Lab Markers):

• Fasting glucose: > 126 mg/dL (diabetes range)
• A1C: > 6.5% (diabetes range)
• Fasting insulin: Very high (> 20 mIU/L)
• Cholesterol: Elevated LDL, low HDL, high triglycerides
• Liver enzymes: Elevated (ALT, AST)—suggests fatty liver

When Insulin Sensitivity is Optimal

Physical:

• Stable energy throughout the day (no crashes after meals)
• Healthy body composition (minimal visceral fat)
• Can go 4-5 hours between meals without intense hunger or irritability
• Stable weight (easy to maintain or adjust with reasonable effort)
• Clear, healthy skin

Cognitive:

• Clear thinking, sharp focus
• Stable mood, emotional resilience

Metabolic (Lab Markers):

• Fasting glucose: 70-85 mg/dL (optimal range)
• A1C: < 5.5%
• Fasting insulin: < 5 mIU/L (optimal)
• HOMA-IR: < 1.0 (excellent insulin sensitivity)
• Triglycerides: < 100 mg/dL
• HDL cholesterol: > 60 mg/dL

Phase Impact

Baseline (Regular Cycle, Pre-Perimenopause): Insulin sensitivity is typically optimal (unless genetic predisposition, diet, or lifestyle factors create resistance). Estrogen supports healthy glucose metabolism. Weight is stable and responsive to diet/exercise changes. Energy is consistent.

Electric Cougar (Early Perimenopause): Estrogen begins to fluctuate, but is often still relatively high. Some women notice early signs of insulin resistance: slight abdominal weight gain, increased cravings, energy dips after meals. This is when lifestyle interventions (diet, exercise, stress management) are most effective at preventing progression.

Wild Tide (Mid-Perimenopause): Estrogen becomes erratic, declining overall. Insulin resistance often worsens noticeably. Abdominal weight gain accelerates. Energy crashes become more frequent. Cravings intensify. Many women struggle with weight gain despite no changes to diet/exercise. This phase requires proactive metabolic support (low-carb diet, strength training, possibly metformin or HRT).

Henapause (Late Perimenopause, 7-11 Months Without Period): Estrogen is consistently low. Insulin resistance may be at its worst. Metabolic changes feel sudden and dramatic. Weight gain feels unstoppable. Energy is low. Blood sugar dysregulation is common. This is a critical window for intervention to prevent metabolic syndrome and type 2 diabetes.

The Pause (Menopause, 12+ Months Without Period): Estrogen stabilizes at low levels. Insulin resistance persists unless actively addressed. Many women are diagnosed with prediabetes or metabolic syndrome at this stage. HRT (especially estrogen) can significantly improve insulin sensitivity. Lifestyle interventions remain essential.

Phoenix Phase (Early Post-Menopause, 2-10 Years After Last Period): Insulin resistance is common and often worsening without intervention. Women on HRT tend to have better metabolic health than those not on HRT. Strength training and metabolic nutrition become even more critical. Cardiovascular and metabolic disease risk increases.

Golden Sovereignty (Established Post-Menopause, 7+ Years After Last Period): Insulin resistance is prevalent, but those who have addressed it proactively (HRT, diet, exercise, medication if needed) often have excellent metabolic health. Those who haven't may have progressed to type 2 diabetes or cardiovascular disease. This phase is about maintaining metabolic optimization for long-term health and vitality.

Testing & Optimization

When to Test

Testing for insulin resistance is valuable, especially in perimenopause/menopause when risk increases dramatically.

Standard tests (covered by insurance, widely available):

• Fasting glucose → measures blood sugar after 8-12 hour fast

  • Normal: < 100 mg/dL
  • Prediabetes: 100-125 mg/dL
  • Diabetes: ≥ 126 mg/dL

• A1C (hemoglobin A1C) → measures average blood sugar over past 3 months

  • Normal: < 5.7%
  • Prediabetes: 5.7-6.4%
  • Diabetes: ≥ 6.5%

• Lipid panel → cholesterol, triglycerides, HDL, LDL

  • High triglycerides and low HDL suggest insulin resistance
  • Triglyceride-to-HDL ratio > 2 is a strong marker of insulin resistance

Advanced tests (may require specific request, sometimes out-of-pocket):

• Fasting insulin → measures insulin level after 8-12 hour fast

  • Optimal: < 5 mIU/L
  • Normal: < 10 mIU/L
  • Elevated: > 10 mIU/L (suggests insulin resistance, even if glucose is normal)

• HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) → calculated from fasting glucose and insulin

  • Formula: (Fasting Glucose × Fasting Insulin) / 405
  • Optimal: < 1.0
  • Insulin resistance: > 2.0

• Oral Glucose Tolerance Test (OGTT) → measures glucose and insulin response to sugar load

  • Fasting glucose and insulin measured, then drink glucose solution, then remeasure at 1, 2, 3 hours
  • Shows how body handles glucose challenge (more sensitive than fasting tests alone)

• C-peptide → measures insulin production by pancreas (more stable than insulin)

When to test:

• At perimenopause onset (establish baseline)
• If experiencing abdominal weight gain, fatigue, cravings, energy crashes
• If family history of diabetes or metabolic syndrome
• Annually during perimenopause/menopause (metabolic health changes rapidly)
• Before starting HRT (to assess baseline and guide treatment)

Optimization Strategies

1. Nutrition (Most Powerful Intervention)

Low-carbohydrate or moderate-carbohydrate diet:

• Reduce refined carbs and sugar → bread, pasta, rice, sweets, sugary drinks
• Focus on protein and healthy fats → meat, fish, eggs, nuts, seeds, avocado, olive oil
• Non-starchy vegetables → unlimited (fiber supports blood sugar regulation)
• Moderate complex carbs → sweet potato, quinoa, oats (if tolerated, prioritize post-exercise)
• Low-glycemic fruits → berries (lower sugar impact than tropical fruits)

Why it works: Reducing carbohydrate intake lowers insulin demand → gives cells a "break" from constant insulin exposure → improves insulin sensitivity over time.

Intermittent fasting:

• Time-restricted eating → eat within 8-10 hour window (e.g., 10am-6pm)
• Extends fasting period → lowers insulin levels → improves insulin sensitivity
• Note: Some women feel worse with fasting (especially in perimenopause due to cortisol sensitivity). Listen to your body.

Protein prioritization:

• 1.2-1.6 g protein per kg body weight (or 0.5-0.7 g per pound)
• Supports muscle mass (critical as estrogen declines)
• Protein is the most satiating macronutrient → reduces cravings, supports stable blood sugar

Fiber:

• 30-40 g per day → slows glucose absorption, supports gut health, promotes satiety
• Sources: vegetables, nuts, seeds, avocado, berries, chia, flax

Avoid processed foods:

• Ultra-processed foods are designed to spike insulin and promote overconsumption
• Focus on whole, unprocessed foods

2. Exercise (Essential for Insulin Sensitivity)

Strength training (most effective for insulin resistance):

• 2-4x per week → builds muscle mass
• Muscle is metabolically active → absorbs glucose efficiently, improves insulin sensitivity
• Estrogen decline accelerates muscle loss → strength training counteracts this
• Increases resting metabolic rate → easier to maintain healthy weight

High-intensity interval training (HIIT):

• Short bursts of intense exercise → depletes muscle glycogen → improves glucose uptake
• 1-2x per week (be mindful of cortisol response; too much HIIT can worsen stress/cortisol)

Walking (underrated but powerful):

• Post-meal walks (10-15 minutes after eating) → significantly reduces blood sugar spike
• Low-cortisol, sustainable, accessible
• Daily walking supports insulin sensitivity, cardiovascular health, stress management

Consistency matters more than intensity:

• Moving daily (even moderate activity) is more effective than occasional intense workouts

3. Hormone Replacement Therapy (HRT)

Estrogen therapy improves insulin sensitivity:

• Restores estrogen's metabolic benefits (glucose uptake, fat distribution, inflammation reduction)
• Women on HRT have lower rates of type 2 diabetes than those not on HRT
• Transdermal estrogen (patch, gel) is preferred → safer for metabolic and cardiovascular health than oral estrogen

Progesterone:

• Bioidentical progesterone (micronized) is metabolically neutral
• Synthetic progestins (medroxyprogesterone) may worsen insulin resistance → avoid if possible

Testosterone (if deficient):

• Low-dose testosterone can improve body composition (muscle mass, fat loss)
• Supports metabolic health, energy, motivation for exercise

HRT is not a replacement for lifestyle, but a powerful complement.

4. Medications (When Lifestyle and HRT Aren't Enough)

Metformin:

• First-line medication for insulin resistance and prediabetes
• Improves insulin sensitivity, reduces liver glucose production, supports modest weight loss
• Dose: Typically 500-2000 mg daily (extended-release better tolerated)
• Side effects: GI upset (nausea, diarrhea)—usually improves over time; rare risk of B12 deficiency (supplement B12 if on long-term metformin)
• Benefits beyond glucose: May reduce cancer risk, support longevity, improve PCOS symptoms

GLP-1 agonists (semaglutide/Ozempic/Wegovy, liraglutide/Victoza):

• Originally diabetes medications, now approved for weight loss
• Improve insulin sensitivity, promote significant weight loss (especially visceral fat), reduce appetite
• Note: Expensive, often not covered by insurance for weight loss (though may be covered for prediabetes/diabetes)

SGLT2 inhibitors (empagliflozin, dapagliflozin):

• Lower blood sugar by promoting glucose excretion in urine
• Cardiovascular and kidney protective benefits
• Typically used for diabetes, not prediabetes/insulin resistance

Discuss with clinician to determine if medication is appropriate.

5. Supplements (Supportive, Not Primary Treatment)

• Berberine (500 mg, 2-3x daily) → improves insulin sensitivity (comparable to metformin in some studies)
• Alpha-lipoic acid (300-600 mg daily) → antioxidant, improves insulin sensitivity
• Chromium (200-400 mcg daily) → supports glucose metabolism (evidence is mixed)
• Magnesium (300-400 mg daily) → essential for glucose metabolism; deficiency worsens insulin resistance
• Omega-3 fatty acids (1-2 g EPA/DHA daily) → reduces inflammation, supports metabolic health
• Vitamin D (2000-4000 IU daily, or dose to achieve optimal levels) → deficiency linked to insulin resistance
• Inositol (myo-inositol, 2-4 g daily) → improves insulin sensitivity, especially in PCOS

Note: Supplements are adjuncts, not replacements for diet/exercise/medication.

6. Sleep Optimization

• Poor sleep worsens insulin resistance → aim for 7-9 hours of quality sleep
• Sleep deprivation increases cortisol, ghrelin (hunger hormone), decreases leptin (satiety hormone) → promotes overeating, insulin resistance
• Prioritize sleep hygiene: cool/dark room, consistent schedule, limit screens, address sleep apnea if present

7. Stress Management

• Chronic stress raises cortisol → cortisol promotes insulin resistance, visceral fat accumulation, blood sugar elevation
• Practices: meditation, breathwork, therapy, boundaries, nervous system regulation, joy, rest

When to Review with Clinician

You should discuss insulin resistance and metabolic health if:

• Abdominal weight gain (especially sudden or unexplained)
• Difficulty losing weight despite diet/exercise efforts
• Energy crashes after meals, intense cravings
• Family history of diabetes, heart disease, or metabolic syndrome
• Dark skin patches (acanthosis nigricans) or skin tags
• Acne, facial hair, scalp hair thinning (androgen excess)
• Fasting glucose ≥ 100 mg/dL or A1C ≥ 5.7% (prediabetes)
• High triglycerides, low HDL, or other metabolic syndrome markers
• Interested in testing insulin levels or HOMA-IR
• Considering metformin or other metabolic medications
• On HRT and want to optimize metabolic benefits

Red flags requiring immediate medical attention:

• Fasting glucose ≥ 126 mg/dL or A1C ≥ 6.5% (diabetes)
• Symptoms of very high blood sugar (extreme thirst, frequent urination, blurred vision, unexplained weight loss)
• Chest pain, shortness of breath (possible heart attack—insulin resistance increases cardiovascular risk)
• Severe fatigue, confusion (possible diabetic emergency)

Related Terms

• estrogen
• testosterone
• cortisol
• insulin
• shbg
• androgen-dominance
• metabolic-syndrome
• visceral-fat
• brain-fog
• weight-gain